Thesis--Copenhagen. / Summary in Danish. Includes bibliographical references (p. i-lvii).

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (PH. D.)--Columbia University, 1928. / Vita. Bibliography: p. [28].

Thesis (Ph. D.)--Virginia Commonwealth University, 2006. / Prepared for: School of Medicine. Bibliography: leaves 168-188. Also available online.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 116-121).

The sarcoplasmic reticulum (SR) of striated muscle plays a central role in control of contractile activity. It acts as an intracellular sink for calcium during relaxation and releases cav2 + during contraction. This highly differentiated endoplasmic reticulum is a self-contained network with a continuous hollow interior which surrounds each muscle fibril (Fig. 1) (Porter, 1961). The SR is fragmented at longitudinal intervals of one sarcomere in length by the transverse tubular or T-tubular system (Porter, 1961; Franzini-Armstrong, 1980). On each side of the T-tubules there are enlarged areas known as cisternae, with branched areas between the cisternae known as the longitudinal elements. The juncture of the three membranes (two terminal cisternae and one Ttubule) is referred to as the triad. The junction between the SR and • 0 the T-tubules is known as a junctional gap and has.a width of 100-200 A. Periodic densities, referred to as 'feet', cross the junctional gap to join the SR and T-tubular membranes (Franzini-Armstrong, 1980). Direct communication between the SR, the T-tubules and the feet have been postulated (Schneider· and Chandler, 1973; Mathias et al., 1979). The view has developed, starting with the experiments of Huxley and Taylor (1958) and Huxley and Straub (1958), that, under physiological conditions, contraction in skeletal muscle is triggered by depolarisation of the membranes of the T-tubules. This results in the release of ca 2 + into the myoplasm from its intracellular storage location, the SR, and thus activating the contractile proteins (Schneider and Chandler, 1973). (See Fuchs (1974) and Ebashi (1980) for a review on the possible mechanism involved in excitation-contraction coupling.)

No description available.

Recently, [³H]nitrendipine ([³H]NTD), a substituted 1,4-dihydropyridine calcium channel antagonist, has been used to label in vitro dihydropyridine calcium channel receptor sites in cardiac and smooth muscle, in the brain, and in other peripheral tissues. We have demonstrated the in vivo labeling of [³H]NTD to brain and peripheral tissues. This specific binding is decreased in a dose dependent manner by pretreatment with increasing doses of nifedipine. Thin layer chromatography demonstrates that the bound tritium species is predominantly the unmetabolized, parent [³H]NTD for the cerebral cortex and the left ventricle, whereas in the liver, the main species are metabolites of NTD. The regional distribution of [³H]NTD specific binding parallels that of in vitro studies. Notable exceptions include the aorta, skeletal muscle, and the ileum. The complex hemodynamic effects of NTD may explain differences noted in these in vivo studies as compared to in vitro studies. A highly sensitive assay for dihydropyridine receptors in cerebral cortical and cardiac homogenates using [³H](+)PN 200-110 ([³H]PN), is described. [³H]PN shows 10-12 fold higher affinity for its binding site than [³H]NTD at physiologic temperatures, and exhibits lower nonspecific binding. D-cis diltiazem and verapamil interact with [³H]PN in an allosteric manner. D-cis diltiazem and verapamil decrease and increase, respectively, the K(d) of the [³H]PN-receptor complex without significantly altering the B(max) in both cerebral cortex and heart. The [³H]PN assay is a distinct improvement over the [³H]NTD assay, and should be a valuable tool in the further study of the dihydropyridine receptor binding site. A radioreceptor assay was developed to measure the free (unbound) and total NTD levels in serum. Standard curves are reproducible and linear from 4 x 10⁻¹¹ to 4 x 10⁻⁹ M NTD. The limits of sensitivity of the assay are 0.1-0.2 picomoles/ml. Using equilibrium dialysis, NTD was found to be 93-98 per cent protein bound in human serum. There was no concentration dependency for protein binding from 1 to 100 ng/ml. A pharmacokinetic study in hypertensive patients revealed a peak total NTD serum level at 90-100 minutes. Preliminary studies suggest a possible dose-dependent accumulation of NTD during chronic drug therapy. The in vitro binding of [³H]NTD was studied in deoxycorticosterone-NaCl hypertensive rats and matched control rats. The hypertensive rats showed a significant decrease in brainstem [³H]NTD receptor density as compared to controls after 6 weeks of treatment. There were no receptor alterations in other selected brain regions and the heart. In light of the role of the brainstem in the development of various forms of experimental hypertension, this study provides evidence of selective alterations in the [³H]NTD sites which may be involved in the development of hypertension. Also, this study provides evidence that dihydropyridine binding sites may be under dynamic regulation.

No description available.

Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.